DIP Episode 301 - Diabetes and The USMLEs Part 1

Okay, welcome. This is episode 300 and 1 of the Divine Intervention Podcasts. My name is Divine and today's podcast is going to be visited on a topic that is Incredibly high for the USML exams. I'm going to be calling this diabetes and the USM Ls I hope in this podcast is to cover pretty much everything that you'd expect to see in an MBME question all the way from step one all the way to step three concerning diabetes so that you're pretty much good to go And as a reminder if you're taking the step two-seeking of step three exams I have an MBME Testicking Strategy Score so the 27th of this month from 2 to 4 30 pm Pacific Standard Time I'll essentially have about a couple of MBME style questions I'll use them to go over a systematic process for reading questions answering questions and avoiding pitfalls that many people fall for in the exam and Then from the 20th of April to the 1st of May I am going to be having a 20-hour super comprehensive review course will be covering peeds surgery OBEGINE I am psych Neuro Bios stats ethics Professionalism basically those changes that showed up in November of 2020 last year And also be covering relevant step one content that has made it to either step two ck So it's like a one-stop shop again many people have participated in this course don't extremely well.

I mean I've Again, I'm not going to say like straight up numbers What I know there is a person that has attended my course that has gotten close to a 2-EAT on their exams So the course is really comprehensive and I'm making it better and better and better each time So again, if that's something I'm interested in just shoot me an email and Through the website and I'll give you some more details on cost and things like that and For those of you listening, you know, hopefully in the future I would hold a step one Step one course Probably like sometime around June or something. So if you're interested just shoot me an email and I will guide you in the right direction Okay, so let's go ahead and start right so diabetes right so diabetes is a big big big topic, right? And again, it's something that many people understand the basics for many people again, sadly Don't really understand pathophysiology, right? So let's kind of hit on many of the things with diabetes and again Diabetes is one of these amazing topics where you can do just lots and lots and lots and lots of integration Right, so again, this is a diabetes podcast But again, you will end up learning like a ton of other stuff, right? You learn a ton of other stuff So I'll just encourage you to just be attention Take good notes listen understand this is one of those podcasts.

They want to listen to multiple times I think you're ultimately will ultimately help you okay, so Diabetes right so when all the diabetes is bad Right, I mean it affects many people in the US and it's particularly common in people that are you know African-Americans and it's also common in native Americans And also people that are from Alaska whatever bizarre is in those people tend to have a diabetes, right? And one of the diabetes causes many bad things, right? Diabetes is the thing that makes people blind Makes people blind It makes people have kidney issues makes people have nerve issues, right? And again, you know, we'll talk about the pathophysiology behind many of those Behind many of those things, right? So the thing with diabetes is Essentially the final common pathway of everything with diabetes is the person's blood glucose is Really really high, right? The person's blood glucose is really really high But the way you get there is different, right? The way you get there is different, right? um Essentially your blood glucose will be really really high because you don't have Like you don't have adequate amounts of insulin activity, right? So you may say okay divine How do I get to a situation where I don't have adequate amounts of insulin activity? Well, we'll talk we'll talk about that, right? So usually when the person presents with diabetes, what are some symptoms they could present with, right?

So remember, uh, especially when they present like in these diabetic emergency situations They'll present with polydipsia, right? So you may ask yourself okay divine what's the pathophys there? Well, if a person is not getting adequate amounts of insulin activity Then they will have a lot of glucose kind of strain around in your bloodstream Well glucose is very responsibly active, right? So you can be filtered you get filtered in the kidneys and then If you exceed the transport maximum of those proximal convoluted tubular cells which is right around 180 milligrams. So basically at a blood glucose level on about 180 milligrams per deciliter You exceed the ability of those proximal convoluted tubular cells Those are sglt 2 receptors To reabsorb glucose, right? So glucose will then start showing up in the urine as that glucose shows up in the urine Is going to draw water with it and if you draw water with it well, you're gonna have a lot of You're gonna be pee pee pee pee in a ton well if you pee pee pee pee pee of ton Then sadly you're buddy will be like okay, I need water water water, right? So you're gonna drink drink drink drink drink a ton Right, so that's polydipsia polyurea, right? And these people also have polyphasia. So in fact, I always wondered why do people that have diabetes have polyphasia, right? But again, if you think about it in diabetes again, I said you're not getting an insulin effect Well, what does insulin do?

Insulin is the thing that literally feeds your cells, right? If you think of insulin as a cell feeder, then this polyphasia would make sense, right? Because If your insulin is not around, right? Then you're not feeding yourself, especially like your muscles Right and your adipose cells remember your muscles and your adipose cells are examples of insulin Dependent tissues, right? The examples of insulin dependent tissues In fact when people have diabetes the thing that happens is that The insulin dependent tissue is not getting anything, right? Like Because again, remember insulin makes you put more good for transporters on the surfaces of your adipocytes And your skeletal muscle, right? So if you have an insulin deficiency, then you're gonna be putting good for receptors on your skeletal muscle on adipocytes so those things starve So your body is like man, I'm hungry, I'm hungry, I'm hungry, I'm hungry, right? That's why people that have diabetes Right especially type 2 diabetes, they tend to eat a ton, right? So We may then say okay, so what are the ways that people get what are the different ways that people Kind of gets to kind of gets to diabetes well the person can have type 1 diabetes, person can have type 2 diabetes, right? We know that type 1 diabetes classically on in-beaming exams. You'll present In a teenager, right? It presents in the teenager very young adults, right?

Usually a person that's less than 30 years old And they'll tell you in the question that Well the person has been it can be like a person that develops secondary and uruses, right? So the person out of the blue starts bed wedding, right? Whenever you see stuff like that again, you want to think about a Type 1 diabetes, right? Because again that polyurethane so that kid can start bed wedding Or they can tell you something about the kid like you know, he has lost like 10 pounds or 5 pounds over a very short period of time Haspolaria, Haspolidipsia, right? Whenever you see stuff like that again, want to think about diabetes Especially type 1 diabetes and sometimes the primary presentation of type 1 diabetes can literally be decay In fact, they think about one out of every four people that are diagnosed with type 1 diabetes the first presentation in those people Is a diabetic kidney dosage So you may say okay divine Why what happens in people that have a why do people develop type 1 diabetes? Well they can decay for many reasons, right? So The big big thing you want to remember is inflammation, right? Big big big thing you want to remember is inflammation, right? So the thing is especially for those that are taking step one your friends at the mbme They kind of want you to know some basic science details that on the lie how type 1 diabetes Develops right so for example one thing that can cause type 1 diabetes is If for some reason you have a failure of immune tolerance, right?

Because remember in type 1 diabetes is almost like an autoimmune diabetes They're pretty much just going and destroying the pancreatic Beta-ilett cells, right? So you may say oh what is causing me to destroy the pancreatic beta-ilett Cells well the thing that's causing it is a immune system that normally does not destroy those cells Says hmm this thing looks foreign to me. Let me go ahead and destroy it And one nice integration that you can actually keep at the back of your mind for mbme exams is that people that have type 1 diabetes in some cases They have mutations in a gene that's known as CT LA4, right? CT LA4 if you remember again CT LA4 is one of these genes you don't find You don't see disgusting many in many resources But it's actually high to know for the USM exam especially step one, right? So if you have a mutation in CT LA4 CT LA4 is something that normally suppresses T cells, right? It's one of those mechanisms potentially behind the person developing Self tolerance because again your body your T cells are not supposed to destroy your pancreas. That's literally not the job description So your beta cells right and many cells in the body, right? You but let's you know focus on the beta cells They produce CT LA4 and that CT LA4 tells those T cells. Okay, shut it. Don't come here.

Don't destroy us Right, but if a person has a CT LA4 mutation Then they're not able to tell those T cells to shut it And if those T cells don't shut it they come and destroy the person's pancreatic eyelids, right? So that ought especially the beta cells right so that ultimately causes issues That's how people develop type one diabetes right again. They have like a failure of self tolerance Right in fact classically when you do a biopsy of the pancreas of a patient that has type one diabetes You usually find like a lymphocytic infiltrate. That's a higher factor to know for the exams, right? And again, so if you may be like oh define this CT LA4 is there any other reason why I should keep this Thin in mind well the thing is certain cancers Actually upper-regulate CT LA4 when you operate CT LA4 You're gonna dumb down T cells because remember one of the ways that our bodies Prevent us from getting cancer is that T cells are very good anti-cancer cells, right? So many malignancies especially some lung cancers They do this thing with CT operating CT LA4 So you can essentially neuter those T cells only neuter those T cells They're not gonna come and attack the cancer, right?

That's why we've actually like Meet some drugs I'm not gonna go into that now because that's not the purpose of this podcast But if you think of some lung cancer drugs Especially like you hear of these anti-PD1 agents and all these CT LA4 therapies Um Drugs like new volume up for example These are drugs that all work through that CT LA4 pathway ultimately To you know cause your immune system to be activated so that they can start attacking the malignancy But again, that's a discussion for another day, right? So and the thing is again when these T cells are activated remember T cells can Paralpo partner would be cells You know help them class switch right and then you make antibodies, right? So the thing is if you would have type 1 diabetes they can actually develop auto antibodies, right? You can develop auto antibodies against insulin You can develop all auto antibodies against the pancreatic beta cells, right? So if you actually really think about this because your friends at the MBME They can kind of bring this back to the realm of immunology, right? So type 1 diabetes is actually um a type 2 and a type 4 hypersensitivity reaction The type 4 hypersensitivity reaction part is your T cells during the damage The type 2 hypersensitivity reaction part is to add those auto antibodies that are made That perform a lot of destruction, right?

So that's something that's kind of high used to keep at the back of your mind for exams and Remember that people that again is not just having these gene mutations that can increase their presence risk of type 1 diabetes, right? These people unfortunately also have certain genetic susceptibilities, right? Or environmental susceptibilities So one thing I would just encourage you to keep in mind is if people have like if they have like HLEDR3, HLEDR4 Those things are associated with them are developing type 1 diabetes again It's not everyone that has HLEDR3, DR4 that develops diabetes But if you have that you add elevated risk of developing diabetes, right? So again, remember especially type 1 diabetes I can remember it's not the fact that you just have those things, right? You also need like the right perfect storm of environmental conditions And I know you may be like wow the vine has seen so much about genetics So genetics mostly like a monster role in the development of type 1 diabetes Again, that's true But genetics play even more of a monster role in type 2 diabetes than type 1 diabetes I mean many of these things have been proven by like these twin concordance studies, right? I mean it's roughly about like if you if you have like two twins, right?

And one has type 1 diabetes the risk of the other one having type 1 diabetes about 50 percent But if you have a twin with type 2 diabetes, there is called the other one developing type 2 diabetes about 90 percent So there's a stronger actually genetic basis for type 2 diabetes compared with type 1 diabetes So that's that's kind of like the big big thing with type 1 diabetes And again, remember people that have type 1 diabetes Those people the uponcress has essentially burnt out, right? So the uponcress is burnt out So because the uponcress has burnt out, they're essentially not going to be able to make insulin, right? So really the only treatment for type 1 diabetes for the most part Is to give those people insulin, right? Is to give those people insulin And I mean there are many there are many different kinds of There are many different kinds of insulin, right? There's like You know like the ultra rapid In fact, maybe let me see something about insulin The thing is we know that the way normal physiology works for most human beings Right? Actually for human beings, you know normal person Is that the body does this thing where it has You know if you check a person like a normal person if you check their blood They'll always be insulin in it, right? Because the thing is your cells need a constant consistent supply of glucose to eat, right? So the thing is you have like this basal level of insulin that's always released But then whenever you eat, right?

Whenever you go to a fast food restaurant or you eat at home or whatever Then there's this big spike in your blood glucose, right? So your body like can say, oh you know what? I release these normal amounts of insulin Let me have these big spikes, right? So whenever you eat you have a big spike of glucose And again, what's the thing that controls those So you have that big spike of glucose, so your insulin spikes in return So how does your insulin spike in return? It's true something called an increase in Right? It's true something called an increase in right that increase in is a GLP1 right GL is called GLP1 They actually produce by the L cells in your GI tract, right? So those things the cost some signaling that ultimately causes you to produce insulin in a response to a meal, right? Because you to produce insulin in a response to a meal so When glucose touches your stomach, your small intestine, you stand making all these ingredients That causes you to release insulin, right? And again insulin doesn't just come out of the blue, right? Insulin comes, you know, when you want to release insulin Because remember if you consume glucose, that glucose has to enter the pancreatic beta cells Remember the pancreatic beta cells have a gluten receptor, right?

So the glucose will come in through the gluten receptor Which is bi-directional by the way To the pancreatic beta cells And then those pancreatic beta cells we know that that glucose can be converted to glucose 6-4 feet by an enzyme known as glucose kinase, right? And again all these things you see me saying I'll bring in some integrations in a second, right? So that glucose is converted to glucose 6-4 feet by glucose kinase And then that glucose 6-4 feet, you know, it will go through glycolysis, TCE cycle, electron transport chain You make a ton of ATP Well in a pancreatic beta cell That ATP has the ability to close certain potassium channels When it closes those potassium channels, right? Potassium is not going to be leaking out of the cell anymore So the cell will have a buildup of positive charge and still cause the cell to depolarize When the cell depolarizes then certain calcium channels that are voltage-gated will open, right? So those calcium channels have the ability to open by changes in voltage, right? So if the cell depolarizes the voltage is becoming more positive So that's going to cause those calcium channels to open, calcium will come in, right? And when that calcium comes in, that's then going to cause you to take these vesicles that contain bugs of insulin and then they are released into the circulation, right? And remember whenever insulin is released, it doesn't get released alone It gets released with a bunch of stuff actually, right?

So it gets released, I would say probably like the big thing to keep at the back of your mind is CPAP type, right? So whenever insulin is coming from the body, right? Or from an insulin-based malignancy in the body like an insulin-noma The person's insulin levels will be elevated, the person's CPAP type will be elevated, right? And the thing is insulin and it's leaving the pancreatic beta cell Because those pancreatic beta cells, they actually in the center of the eyelids So it's almost like they secret this insulin and it's like radiating outwards, right? So in the eyelids beta cells that are producing insulin in the center What are the alpha cells that produce glucogone, they actually in the periphery Right? So as that insulin is coming out, it actually hits those pancreatic alpha cells that produce glucogone And inhibits the secretion of glucogone, right? So again, you're making insulin, you're making CPAP type, right? So if for example a person, you know, classically an MBME exam So it'll be like a healthcare worker or a medical student or a nurse of some sort And you're noticing that he keep having all this hypoglycemia, right? And then you see something about, you know, maybe this person has like a psychiatric history, right? And then you can tell you the question, wow, this person's insulin is elevated But the CPAP type is undetectable Whenever you see stuff like that, right? You want to think about fictitious hypoglycemia, right?

The person is essentially just making up symptoms, right? So that they can, you know, they want to essentially draw attention to themselves, right? So that's fictitious hypoglycemia, right? So you know, they'll have whipols tried, whipols tried again, many people know this is pretty obvious, right? It's a pretty obvious try, right? You'll have hypoglycemia, you'll have signs of hypoglycemia, and you'll have relief of symptoms, right? With glucose administration So the fact that the insulin is high and the CPAP type is undetectable, that tells you that Okay, this person is probably making up their symptoms in some way, shape or form, right? This person has become of symptoms in some way, shape or form But you know, if you see an elevated insulin and a little bit of CPAP type Well, that means the insulin is coming from within the body But the thing is insulin can come from within the body from natural processes, right? Or it can come from cancer like an insulinoma, right? Or it can come from you forcing your body to make higher levels of insulin that is normal, right? So see for example, a softener urea, right? Because if you remember, we can talk about how ATP blocks those potassium channels that we find on the in the pancreatic beta cells, which will cause the cell to depolarize And then voltage to the calcium channels will open, bringing calcium and any secret baths of insulin, right? So, softener urea is essentially blocked at potassium channel, right?

To cause you to release a ton of insulin That's also the exact, so softener urears, right? So things like clopropomide, tubularide And then there is, I think like the second generation ones like gluburite, glipeside, glimipride Right? Those things all work by blocking potassium channels And by the way, there's also a group of, I almost call them like non-sophonial urea, softener urears, right? So these are drugs like your miglidinites, right? They called miglidinites, repaglinite, and antagonite Those things also block those potassium channels But the thing is they are a little more rapid acting than the regular softener urears So those things because they block those potassium channels, they can cause you to release a ton of insulin They can cause you to release a ton of CPAP type, right? So the thing that will happen in those circumstances is People that are abusing softener urears because they'll be like, Oh wow, the healthcare system is smart, they will check my CPAP type levels, right? So those people, right? They're essentially taking an insulin secretor gunk, that's a buzzword you want to recognize for Mbim exams, right? Like a softener urea or miglidinite, right?

So the insulin is elevated, the CPAP type is elevated, so it may say okay to find, So how am I going to differentiate these people from people that have like some kind of insulin Well the way you're going to make that differentiation is by doing a secretor gunk screen It's essentially like a blood test for softener urears, right? So the insulin will be elevated, the CPAP type will be elevated, but They will have like a positive blood test that, oh, these people are taking some kind of secretor gunk like a softener urea or miglidinite and then you essentially catch them in the act, right? But again, that's not the only direction your friends at the Mbim can take with these CPAP types If you remember I'm essentially discussing the different Mbim contexts for CPAP type levels, right? One thing you want to keep in mind is actually different, shelling between type 1 and type 2 diabetes literally by CPAP type levels, right? For the most part people that have type 1 diabetes, the pancreas is essentially the beta cells and the pancreatic highlights are burnt out, right? So those people, again, they are not making insulin, if they're not making insulin, they're not going to be making CPAP type. So in type 1 diabetes, the CPAP type levels are actually low, right? In fact, one experiment, because again, remember your friends at the USMLE that write these as step 1 exams, they love to write these experiment-based questions.

They can actually give you a question about a person and they are trying to establish the diagnosis of that type 1 diabetes, right? And then they will see which of the following is the expected result with glucagon infusion, right? I would hope you're telling me that, oh, divine, if a person is a type 1 diabetic, diabetic, if we give them a glucagon infusion, their CPAP type levels will fail to rise. So what's the what's the pathophysiology there? Well, again, if you give a person glucagon, glucagon is a counter-regulatory hormone, right? So it's going to raise the person's blood glucose levels. If the person's blood glucose goes up, right? That's going to cause, that's going to trigger a release of insulin, right? And as insulin is being released in higher measure, CPAP type will be releasing higher measure. But if your pancreas is not working for whatever reason, right? Then you're not going to be able to have that response, right? So whenever you see a person where, oh, you give them a glucagon infusion, like they give you an experiment-based question on the exam, the person gets a glucagon infusion and their CPAP type levels fail to increase a glucagon infusion. That's a pretty good diagnostic test for type 1 diabetes on NV Me exams. Although, again, there are many other things we used to diagnose diabetes in folks, right? Well, again, if a person has type 2 diabetes, right? They have like insulin resistance, right?

And again, I know I haven't talked about type 2 diabetes. They're just some quick integrations I want to talk about before I keep going. But people that have type 2 diabetes, they have, at least, especially like in the early phase of disease, they have insulin resistance. So they're making a ton of insulin, right? That's a ton of insulin they're making. It's going to be made with a ton of CPAP type, right? So again, CPAP type levels tend to be high in people that have type 2 diabetes, but tend to be low or non-existent in people that have type 1 diabetes, right? And again, some other integrations I just want to kind of talk about along the way, right? I talked about how impritence can cause you to release more insulin, right? GRP1 is the chief of them all, right? Remember, those impritence, we can actually make pharmacological incretions, right? Those GRP1 agonists, right? So drugs like exenatide, lyraglutide, right? So those things, they cause you to literally make more insulin, right? So that's why those drugs can actually be used in type 2 diabetes, where your pancreas is actually still working, right? Remember those exenatide lyraglutide, they actually cause weight loss. And the reason there is that those things, they actually decrease your gastric emptying, so they give you that sense of feeling full very quickly, right? So you don't eat as much, right? So those things can actually cause weight loss.

In fact, I believe a lyraglutide has been approved by the FDA for weight loss. Another thing that can also do to, you know, increase your incretions, right, is to decrease the activity of the enzyme that breaks them down, right? The enzyme that breaks down in critins, the literally enzyme that breaks down GRP1 is called DPP4, dipeptidyl peptidys 4, right? So that can tell you that it's something that cleans up peptide bonds, right? So there are DPP point inhibitors that also diabetes drugs, right? So drugs like, um, drugs like, um, they are the glyptins, right? Like aloe glyptin, lena glyptin, sacsaglyptin, cedar glyptin, right? Those drugs are DPP point inhibitors, by being DPP point inhibitors, they essentially decrease the breakdown of GRP1, right? So GRP1 can do its job. Now, the big thing with these drugs that's like a subtle difference, but it's kind of high on is that these drugs actually weight neutral, right? They're not like the GRP1 analogues, they are weight neutral. But one thing I'll just say is GRP1 analogues, right? Remember, those things can actually increase the presence risk of pancreatitis, right? So if a person has a histrovalcoholusin, that may be a relative contraindication to those on MBME exams. And also if a person has a histrovalcoholusin, if a person has a histrovalcoholusin, a medallary thyroid cancer, or some disease that predisposes them to medallary thyroid cancer, so like ME and any of those ME and two syndromes, right?

Those people should also not take the GRP1 analogues. I believe, uh, as those drugs were being made, um, I think there was an increased uh, incidence of medallary thyroid cancer in rats that were exposed to those drugs. So that's why there's that warning. I believe from the FDA. Um, and then I've kind of talked about how sulfonibrias, right? Again, they're pretty great for, um, you know, they block those potassium channels that we find in the pancreatic beta-ilett cells, right? By blocking those potassium channels, right? The cell will depolarize and make more insulin. So if you really notice when a person is taking the sulfonibrias, they're literally taking a, uh, they're literally giving themselves insulin, right? Uh, so sulfonibrias should make sense that it caused weight gain, right? So you may say, oh, define, okay, why is that weight gain? The thing is insulin is literally a growth factor, right? Like insulin makes your muscle cells, right? Again, you put more blue-four transporters on your surface, you're bringing more glucose, right? So it makes your muscle cells grow, right? But also another cell type that, you know, has blue-four transporters that you add, addypocytes, right? So you addypocytes, they have a lot of, uh, yeah, you addypocytes are insulin-dependent tissues, right? So, uh, as you put more blue-four receptors on your surfaces, right? You're gonna bring in more glucose, right?

And that glucose, you know, again, ultimately, ultimately can be made into fat, right? So again, you can see you're, you're, you're basically like increasing the size of your addypocytes, right? So as you have more and more of that, right? Again, that's gonna make you fat, right? So, um, um, so many areas, they, they, definitely cause weight gain, they definitely cause weight gain. Um, and then on those potassium channel businesses, right? I mean, many of us, you know, have probably memorized that some point in the past, or the thiazides cause, you know, hypergluc, right? You know, many people know that the, oh, they cause hyperglucemia, hyperlipedemia, hyperlerosemia, um, hypercalcemia, you know, I'm not gonna explain all those things. I'm just gonna explain the endocrine-relevant parts, but the thing is thiazides, one thing they actually do is, they actually open up potassium channels, thiazides are potassium channel openers, right? So, if you're potassium channel opener, you open up those potassium channels that we find in the bacredit bitters cells. I don't know, you're making more potassium leak out, so that's, it's not gonna depolarize. So, you're not gonna release insulin, right? So, when you take a thiazide, you can develop almost like a relative insulin deficiency, and if you're insulin deficient, you can already begin to see that, okay, you're not gonna be able to go lead to your blood glucose well. So, you're gonna get hyperliceemia, right?

And if you're insulin, um, um, deficient, again, your adipose cells are not gonna be able to glucose, and because remember, one of the things insulin also does is it actually, uh, activates lipoprotein lipase, right? So, that you can bring in uh, free fatty acids, and one of these siglicero into the adiposeye, right? So, and stop fat. So, basically, like if you have an insulin deficiency because you open up potassium channels with a thiazide, you can already begin to see that, oh, wow, I'm not gonna be able to bring in free fatty acids. So, those fats are just gonna hang out in your blood, right? So, you're gonna get hyperlipidemia. And then, uh, you know, we know that thiazides, well, that potassium channel opening effect is also, you know, kind of good, because if you open up potassium channels, right? Especially like in the, like the cells that line your blood vessels, right? That's gonna cause those blood vessels walls to relax, right? So thiazides have a visodilitary effect, right? That's actually why they're, that's one of their blood pressure lowering effects. So, many people just think, oh, thiazides are diuretics. Yes, that's true. They make you lose fluid. So, you know, your blood volume goes down, blood pressure goes down, but they also have a visodilitary effect.

That's why usually, uh, on USML exams, they'll tell you that when a person is taking a thiazide, it's maybe not the most genius idea in the world for them to be taking an NSAID, because an NSAID is essentially gonna blunt those effects, those visodilitary effects of thiazides, right? Because NSAI Ds, right, by inhibiting cycloxygenase, your, your, your, persteclanelene levels will go down, right? So, you're gonna get like a visodilitary effect, right? And they remember thiazides, right? Like, they literally excrete it, they compete for the scene transporters that help you get rid of uric acid, right? In the nephron, right? So, uric acid will build up because it's not being excreted, and it's no more rich, right? So, you get hyper urocemia. The hypercalcemia is more of a complicated mechanism. Believe I've discussed that in my renal, in my renal reviews, uh, and I have renal from a colgipot gas, so I'm not gonna go into that, but thiazides definitely cause hypercalcemia, right? And then, um, so those are all, you know, kind of like high-o-things to kind of keep at the, keep at the back of your mind, uh, all these different, uh, all these different integrations. In fact, one integration, like anyone mentioned, right? Like, uh, many of us think of glucokinies, right? I said that glucokinies is specifically found in the pancreatic beta-inlet cells, you know, you can find it in many other places, right?

Um, but, you know, let's talk about it in the context of the pancreatic beta-inlet cells. That glucokinies, right? It literally converts glucose to glucose to six-force fit, right? But again, after you made that glucose six-force here, you make ATP, that will block those potassium channels and they make your yeast insulin. Well, if you kind of think about it, let's assume a person has a glucokinies mutation, right? Where it has like a loss of function mutation, um, or you have a mutation where, you know, it's not as sensitive to glucose. Now, you can really begin to imagine that, wow, this person will need higher than normal levels of glucose to trigger the same release of insulin. So let's say, oh, if your glucose was like 200, you start like, unless it, let's not go already close here. Let's see, your glucose was like 100. That's triggers release of insulin. But because you have a glucokinies mutation, you know, it's not very sensitive. Remember, glucokinies is like a glucose sensor, right? And you have like some gene mutation, right? And it's not like super, super, super sensitive, right? Then you're not going to be sensing glucose levels. So let's see, maybe your block glucose levels of 100 triggered glucokinies activity, but now is taking a block glucose level of 250 to trigger glucokinies activity. Then you're going to have periods in your life where your glucose is really high, but you're not secreting adequate amounts of insulin to deal with that problem, right?

In fact, that glucokinies mutation is something that's essentially the pathophase in many cases of maturity on said diabetes of the young, right? And also pregnant people that have diabetes, like gestitional diabetes, that glucokinies mutation is one pathophase behind that, right? So that's kind of like a nice way to integrate that there. And although, I mean, you should also think about it. Another thing that makes people that are pregnant more predisposed to diabetes is this hormone that's made by the placenta, right? Human placenta lactogen, that human placenta lactogen, right? It's a diabetes genica hormone, right? So it causes these people to be predisposed because, I mean, again, that makes sense, right? Because you're trying to be that you want to have like higher than normal levels of glucose in your blood if you're pregnant, right? So that that glucose can be available to cross the placenta to feed baby, right? So that will make sense. And you know, when you're pregnant as well, you also have very high levels of progesterone, right? When your progesterone is really high, progesterone is also the abelogenic, right? So it raises a prescience blood glucose levels, right? And projecting, you know, one of the reasons why pregnant women need love, love, love, love, love to eat, right? As a pregnant woman, you're like eating up a storm. In fact, this is one of the reasons why there's this projecting analog is called majestral acetate.

It's actually used in people that have cancer, like cancer related cacexia. You can use that to actually spur some of those people's appetite, right? So with all that said, right? So that's essentially the big path of is behind type 1 diabetes and in all those integrations I wanted to make. And again, I said type 1 diabetes, we should do it insulin, right? Should do it insulin, right? And that insulin, again, there are many types of insulin and I kind of talked about the way the body works with insulin, right? We said, I think that was how we went down this inquiry 10, like just mountain. We said that, you know, you have a basal level of insulin, right? And then you have like insulin spikes when you eat a meal, right? So that kind of tells you why, again, type 1 diabetic, they can only, the insulin is the only treatment for type 1 diabetic, right? So those people, they will have a lot of like, so the way you usually treat them, right? You can try to give them like a basal level of insulin, right? Those basal insulins, the last very long, they have like almost like literally no peak, right? They're just basally there, right? These are things like glargine, things like datamir, datamir spelled D-E-T-E-M-I-R. And then another one mission and exam that you don't find in many resources is degludeck, D-E-G-L-U-D-E-C, right? So glargine datamir degludeck, right? Glargine datamir degludeck, right?

And then usually for those people, you go ahead and then give them like insulin that they take with meals, right? Because again, you're giving them that basal insulin, that's good. But again, when they eat, they need an insulin spike. Because remember, these basal insulins don't spike, they don't have peaks, right? So you need to give them an insulin that peaks, right? So usually you give them like an ultra rapid actin insulin, these are things like lespros, aspart, glolicin, glolicin is spelled G-L-U-L-I-S-I-N-E. Aspart is ASP-A-R-T, Lisp-RE, L-I-S-P-R-O, right? So you give those things, right? So the lespros, perblolicin, they're super, super rapid acted insulin, that's what most people take when they're, you know, about to eat, right? Because those things, you know, they peak very quickly within, I think, about 15 minutes of taking them, right? And the adoration of action is like, you know, maybe like two to four hours roughly, something like that. You don't need to memorize those specific numbers for your USML exams. But then, the other kinds of insulin, though, right? You know, besides the ultra rapid acting insulin, there's the regular insulin. Regular insulin, sometimes it's called rapid acting insulin, right? Regular insulin is actually kind of high out on MBME exams for certain reasons, right? So one is cheaper than ultra rapid acting insulin. But that's actually the only insulin that you can give IV, right? That's literally the only insulin can give IV.

And that's actually the one we use in DKA and HHCNS management, right? So when a person gets insulin regular, you're literally managing their DKA and their HHCNS. And then, if a person has, you know, there's another kind of insulin called MPH. MPH is what sometimes you can, it's original action is about two hours. It's cheaper than the basal insulin that's large in DKA, DERAMIER business. So sometimes some people take like MPH twice a day to cover them for 24 hours as that basal insulin, right? But again, the ideal thing for diabetes is to get the large in DERAMIER DERAMIER DERAMIER plus the ultra rapid acting, right? To more closely replicate normal physiology, essentially, right? So and again, because typone diabetes is an autoimmune disease, right? Again, those people can have autoimmune diseases in the MBME question you get, right? So they can have like Hashimoto's, they can have like Adacens, they can have like Videoligo, they can have Prinitius and Lemia, right? This is almost like a construct that the MBME uses. Whenever they give you a question about a person that has an autoimmune disease, go ahead and check the question. Most of the time, maybe like 80% or something like that. Those people also have some other autoimmune disease kind of going on in their lives, right? So that's all I think I'm going to see with typone diabetes, right? So let's go ahead and talk about type two diabetes, right? Let's talk about type two diabetes, right?

So again, I've kind of introduced it a little bit already, right? I said that, you know, this one has a much stronger genetic predisposition compared with type one diabetes, right? Again, I talked about those twin concordance studies, right? And the big thing with type two diabetes is you just have bad insulin resistance, right? So like insulin is around, but it's not working, right? Your body is very resistant to that insulin. And again, many people just memorize, oh insulin resistance, insulin resistance, insulin resistance, yes, that's great. But that's not the only, like you've got to understand the little path of it's here, right? So remember that insulin works through tyrosine kinase receptors, right? Insulin works through tyrosine kinase receptors. So the thing is insulin since it works through tyrosine kinase receptors, if you have like mutations in those receptors, right? And you're not going to be getting that insulin effect, right? So even if insulin is around, if you have a receptor defect, right? And you're not going to be getting those effects from insulin, right? And you know, if you don't get those effects from insulin, right? Again, we said that insulin, one of the things it does is it causes your muscle cells because your muscle is an insulin independent tissue, right? It causes your muscle cells to take up glucose, right? So they can store it as glycogem, right?

So again, your muscles, if there is no insulin around, your muscles are kind of starving for energy because they're not able to get in glucose. So your muscles start depending on alternate forms of energy, right? To get, you know, basically to work, right? So one thing that muscles can use because they have it at baseline, you have a lot of protein, right? So they can break down, break down, break down, break down your protein, right? They can break down your protein. Again, another thing insulin does is it causes your adipose cells to take up glucose so that you can ultimately make it into fatty acids. But again, we said that insulin activates lipoprotein lipase, right? So because it activates lipoprotein lipase, it essentially helps you break down triglycerase that you find fluid in the bloodstream. In two months, you see with glycerol and two free fatty acids, you know, kind of gets into the adipose cell and then you make fatty acids, right? But again, insulin also operates the production of fatty acids, right? I mean, we know that there's this enzyme, right? Called acetylquakerboxylis. Remember, that's the real limiting enzyme of a fatty acid synthesis. Insulin actually activates that enzyme, right? So insulin does all this stuff and you insulin also even makes yourself stick up amino acids so they can make like polypeptides, right? So the thing is when a presence insulin doesn't work, then they're going to basically have the reverse of all those things happening, right?

In fact, all these counter-regulatory hormones will start holding sway. So what are those counter-regulatory hormones? These are things like glucagon, these are things like epinephrine, right? So glucagon epinephrine, they'll start holding sway. And we know that those things, right? They promote like breakdown of fatty of a triglycerase into free fatty acids, right? And as you break down triglycerase into free fatty acids, those free fatty acids can undergo a bit of oxidation, right? And if you have a lot of bit of oxidation, you would already begin to see that, wow, you can make a ton of acetylqua, well acetylqua is used to make ketone bodies, right? So you can see why people, especially people that have type 1 diabetes, those ketone bodies, right? So things like acetylqua, and you do need to know the specific identities of ketone bodies, not just for step 1, but step 2, step 3. So things like acetylqua, things like beta hydroxybutyrate, right? Sometimes even acetylqua, right? So you make all those ketone bodies, right? And that's the thing that can essentially throw you into decay, right? As a diabetic, right? Throw you into decay as a as a diabetic, right? And again, that acetylqua, which again is a ketone body, that acetylqua, is the thing that in some cases, you see some people that in decay, and they have like this 40 order to their breath, right? That 40 order to their breath is essentially acetylqua, right? And you can already begin to see, right?

Because you're forming these ketoacets, right? You're essentially increasing the number of on a countet for anions in your body, right? So those people develop a high anion gap metabolic acidosis. So the body will be like, okay, let's try to compensate, let's let's try to compensate, right? So the way your body will try to compensate is to like, okay, you know what guys, let's blow off a ton of CO2, let's end user respiratory acidosis, right? So the thing is, those people try to start to know these deep breaths, deep breaths, right? That's what's called a kosmol breathing, actually, right? Remember, kosmol breathing is not the same thing as kosmol sign, you don't want to mix those things up on an NBME. Kosmol sign is something we'll find in people that have a constructive perioditis on NBME exams, but again, that's not the goal of today's discussion, so we're going to keep going, right? So that's why these people get all these problems, right? And in fact, if you know about these counter regulatory hormones, right? I said glucogone, I said epinephrine, cortisol is also a counter regulatory hormone, right? And in fact, there are many other things that can cause diabetes besides just like, you know, these things I'm talking about with type one versus type two or whatever, right?

Like if a person has a pushing syndrome for many cause, you know, because they're taking chronic glucocorticoids or they have small cell lung cancer that's producing a topic, CTH, or they have like a cortisol secretion at a normal or whatever, right? Those people literally can develop diabetes, right? And also people that are stressed, right? Because think about it, when you're stressed, what we're going to do in a recent, you're going to release a ton of cortisol, right? You're going to release a ton of cortisol. And again, cortisol is a diabetes genocormal, right? That's why people that are on the chronic levels of stress, they tend to have, you know, bigger BMI's, obesity, high incidence of diabetes. Again, it's not a mistake that when people get into med school, the vast majority of them is only if they have like, you know, very strong personal discipline, they gain weight, right? Again, you're not gaining weight because of like for fun. No, you're gaining me because you under like just very high amounts of stress. Again, the US medical system, just the way it's set up, it's not the most ideal from a lifestyle perspective. Again, I feel like there are many changes that would be made to just the whole US medical system. I mean, I read something on Reddit, Reddit, I'm talking about the person taking their life because they didn't match. Again, many people have taken their lives because they didn't match it. We really shouldn't be having those kinds of things happening.

The US healthcare system, especially the medical education system really needs a lot of change, really, really needs a lot of change. But that's a, that's a, that's a totally different conversation here. So cortisol is a bit of a genoc acid, right? Growth hormone, right? I mean, think about it. Growth hormone, remember when you release growth hormone, it goes to, it causes you to make this thing called IGF1. What do you think IGF1 stands for? Insulin-like growth factor, right? Insulin-like growth factor, right? So the thing is growth hormone, right? It's actually involved in reason, a person's blood glucose levels, right? So again, it's the abitogenic in a sense, right? And also, many other things can cause diabetes, like they can give you a question about a person that has high glucose levels. But then the tell you that, oh, the on abdominal lexory, you can see castifications around the pancreas. Well, that person has chronic pancreatitis, right? For a person has chronic pancreatitis, yeah, pancreas essentially burned out. Well, there's no source of insulin, they're essentially going to have diabetes, right? If a person has a glucogonoma, right? Think about it, when you have a glucogonoma, we literally just said that glucogon is a counter-glittery hormone, right? Your glucogon is going to go up, right? And that's again, going to cause you, because again, glucogon causes you to operate the breakdown of glycogen, right?

Glycogenolysis, and it also increases gluconeogenesis, right? So again, all these things that get towards, including your increasing your blood glucose levels, right? So usually in the presence of the hazard glucogonoma, you know, they'll have diabetes, and then they'll have the skin rash, right? That we call necrolitic migratoryory female, right? If a person has mumps, again, mumps, the virus, again, think about it, mumps is a viral infection. How does your, what, what, what, what, what, what, arm of your immune system responds to viral infections? It's T cells, right? So when a person has mumps, remember, mumps loves to infect the pancreas. When you infect the pancreas, you can get a very powerful inflammatory response from T cells, and that can recover, can destroy the pancreas. That can ultimately lead the person to developing a diabetes, right? So there are many things that can cause diabetes, right? If a person has hyperthyroidism, right? Again, thyroid hormone increases the person's blood glucose levels, right? Again, that that can ultimately, that can ultimately cause, that can ultimately cause diabetes for, for a patient, right? Or if a person has cystic fibrosis, think about it, right? For a person has cystic fibrosis, they're not going to be able to, um, uh, secret pancreatic stuff, right? And, you know, secret enzymes out of the pancreas, those enzymes, they are very toxic. They will auto digest the pancreas. If a person's pancreas is gone, well, guess what?

You're not going to be able to, um, making solid, right? So they're going to develop up, you're going to develop diabetes as, as a result of that, right? So these are just all things that can cause diabetes on an end-bimic exam. I mean, to be honest with you, in my heart and in my soul, I'm almost certain that this podcast is going to need to, it's going to need to pack parts. There's just so many things you can integrate with diabetes, and these integrations, I'm not saying them because I just want to make integrations, I'm saying them because they show up on exams, right? And again, the thing is when you have these integrations, when you have all these different contexts for the material, it's just much easier to remember. And the thing is, it doesn't matter how hard the question you write for you gets, you'll be able to figure out exactly what they're going after, right? Because the understanding is there, right? So again, I always tell my students this, when you're learning, try to make sure that you're making integrations, you're learning these contexts and things like that. That's why I love to make my podcasts in this, in this fashion. Again, it may seem a little unscripted, which is true for the most part, right? But it's a great way to learn, right? That's why, again, thankfully, I still remember many of these things, right? That's why I still remember many of these things. So I said that, you know, I've kind of talked about the path of physiology behind decay.

And again, how all these counter-regulator hormones are holding sway. And then the person gets in, ultimately gets in, gets in trouble, right? So the thing with these counter-regulator hormones, maybe like, okay, divine, why are these counter-regulator hormones are holding sway? Well, again, remember the thing I said at the very beginning about how these pancreatic beta cells, these are including insulin. And that insulin on its way out of the eyelids, shots down local hormone production. Well, if a person has like type 1 diabetes, for example, the literally I'm not making any glucagon, I mean, glucagon is going to be secreted in very high amounts, right? Because, again, there's no insulin to inhibit it, right? So that can cause problems. But also if you're stressed, right? So usually many times the thing that flips people into decay is either they don't take that insulin. I mean, again, obviously, if you don't take your insulin, your glucagon is going to be really high. But if you're stressed for whatever reason, so let's say the person has really severe illness or the person exercises or the person, no, let me not say exercise, but if a person has really severe illness, right? Or they have big stress of some sort, that's going to make them make a ton of cortisol, right? That's going to, again, cortisol is a diabetes or genic hormone, right? So those people are going to have high levels of glucose, right? That's going to cause problems, right?

And again, we remember that glucagon especially, right? Glucagon especially, right? Glucagon especially causes you to break down glycogen to form glucose, right? And again, it also encourages fatty acid breakdown, bidoxidation, right? And all that stuff, right? In fact, if you think about the real limiting enzyme of bidoxidation, right? Carnitin isol transferase. Sometimes you may see some maybe in the exams call it a carnitin pometoial transferase. I remember it's inhibited by malono coe, right? But again, how do you make malono coe? You make malono coe because insulin is promoting fatty acid synthesis, right? So again, if you have no insulin, you know, making malono coe, there is no inhibition of carnitin isol transferase, right? So again, you're going to be promoting betaoxidation, right? So again, you're going to be forming all these ketone bodies. So you see glucagon is a place of big role in this, right? So that kind of explains why people that have type 2 diabetes, where they still have adequate, you know, they still have insulin around. They may not necessarily go all the way to ketone body synthesis because again, remember ketone bodies come because you've done a lot of betaoxidation of fatty acids. You've made a ton of acetylicoe. And in that acetylicoe is used to make ketone bodies.

So people that have type 2 diabetes, at least when the apancras does not completely burn out, that insulin they have is typically sufficient to inhibit the production of glucagon, right? Or at least bring down its activity. So they don't make all that acetylicoe so they don't really make ketone bodies, right? That's the thing that creates this thing called hyperglycemic, hypokitotic, whatever, blah, blah, blah, blah, sticky. It's called HHNS, HHN, HHNK or whatever. You can look up what it means. That's not the main subject of this discussion, right? So that's why those people do not go into ketosis, right? That's why those people do not go into, do not go into ketosis, right? So we see that again, when your body notices that, wow, I'm not getting any insulin effect, I'm not getting any insulin effect, I'm not getting any insulin effect. What is going on here? What's going on here? So your body is like, okay, let me keep secretion as much insulin as possible, secretion as much insulin as possible. Well, the thing is, if you keep secretion as much insulin as possible, again, we said that as you're making more and more insulin, you're making more and more CPAP type. But I'm not thinking that you're making more and more of, as you secret a ton of this insulin, is something called amylene, right? Is something called amylene, something called amylene. The thing is that amylene, you can already begin to see that it kind of sounds a lot like amyloid, right?

So that amylene, as you secret, secret, secret more of it, that amylene can begin to form these like bitter-plated sheet structures, you know, essentially begin to polymerize, and it can form amyloid. And that amyloid can deposit in the pancreas, right? That amyloid can deposit in the pancreas. And when that amyloid deposits in the pancreas, right? Again, you can have this apograin by your friends with congruert steamy. Over time, over time, the presence, because again, amyloid rate is not good. It makes whatever deposits in like dysfunctional. And as you make those things dysfunctional, they stop working, right? So the thing is over time, those people's pancreas can burn out. And if you burn out the pancreas, at some point, you're going to stop making insulin, right? So that's why many times if a person lives for long enough with type 2 diabetes, especially if they're not controlling things well, they're going to ultimately form, form amyloid in the pancreas, burn out the pancreas, stop secreting insulin, right? And then over time, you then start having to give those people insulin, right? And that, because again, many of the problems with type 2 diabetes are, again, I'm not getting that insulin effect, because you have like a receptor mutation or whatever, the thing that usually happens in type 2 diabetes, we usually tend to give these people at least to start metformin, right? Metformin is a drug that actually raises a presence insulin sensitivity, right?

Metformin is a drug that raises a presence insulin sensitivity. And by the way, metformin is one of those drugs that also causes weight loss. Remember the other one I said that causes weight loss, where your, I don't know, I think, where your GLP one aggregates, right? Like exenatidelyreglutide, right? Metformin also causes weight loss, right? Metformin actually increases insulin sensitivity. So it may be like, hmm, divine. How does metformin increase insulin sensitivity? Well, the thing with, the thing with metformin is that metformin actually has the ability to activate something called an AMP kinase, right? So metformin actually increases the activity of something called AMP kinase. So you may say, oh, divine. AMP kinase, how is that helpful? How is that helpful? Well, the thing is AMP kinase actually, you know, through some signaling, because again, remember kinases, their job is to phosphorylate enzymes, right? When you phosphorylate another enzyme, in some cases, it can lead to its, it can lead to its activation, right? So the thing is AMP kinase phosphorylate certain enzymes, and those enzymes, their job is to inhibit the activity of phosphorylate pyruvate caboxykinase and glucose-6 phosphatase, right? And we know that these are like literally legit enzymes that are necessary. Remember, phosphorylate pyruvate caboxykinase literally converts to, I believe, oxaloacetate to phosphorylate pyruvate, right? Remember, that step uses GTP, right?

So if you inhibit that, you inhibit one of the key steps of glucose-neugenices. Remember, glucose-neugenices, you know, can start with pyruvate, right? Pyruvate, you know, pyruvate caboxylics will convert it to oxaloacetate and acyruc will actually activate that process. And then that oxaloacetate is then converted to phosphorylate pyruvate by Pepsi-K, right? Again, phosphorylate pyruvate caboxykinase, and then you make a, you make a phosphorylate pyruvate, and then, you know, it keeps backtracking until you get to glucose-6 phosphate, and then glucose-6 phosphatase, which is in the endoplasmic reticulum, will convert the glucose-6 phosphate to glucose. So the thing that happens is that when AMP kinase, right? So, my phone is an AMP kinase activator, when you activate AMP kinase, AMP kinase will phosphorylate certain enzymes that will lead to an inhibition of phosphorylate pyruvate caboxykinase and glucose-6 phosphatase, which are key enzymes in glucose-neugenices, right? So if you inhibit those enzymes, then glucose-neugenices, which predominantly occurs in the liver, right, doesn't work anymore, right? And if it doesn't work anymore, right? You can see that, oh, yeah, essentially calling off one pathway that could potentially raise your blood glucose levels, right? So that's essentially the mechanism behind metforming being good at increasing insulin sensitivity, right?

And again, because we also do glucose-neugenices in the kidneys, we can see that metforming can potentially be never toxic, in fact, when a person's kidneys don't work, you don't want to give those people metforming, right? Or if you're even putting a person like, they love to give these enemy questions where a person is a diabetic, is admitted to the hospital, and let's see, maybe they have a PE or whatever, right? And you're about to start them on some, you want to maybe do a CT angiogram or whatever, right? Before you give a person a urinated contrast, you need to go ahead and stop their metforming, right? Because again, a donated contrast can cause issues with the kidneys, right? So that can, again, raise the person's risk of metforming toxicity. And again, metforming, I said causes weight loss, but what is one of those big, big, big, big things with metforming, right? In terms of toxicity, metforming, in terms of toxicity, one big thing to keep at the back of your mind with it is the fact that it causes a lactic acidosis, right? So you may see, oh, divine. Why can people get a lactic acidosis with metforming? Again, it all goes back. It's not something you just need to memorize, right? It's not something you need to memorize. It's something that you should understand, right? The thing is, if you inhibit hepatic gluconeogenesis by mechanisms which we've essentially described already, you can already begin to see that the Chorice cycle is not going to work, right?

So what in the world is the Chorice cycle? The Chorice cycle is if you're exercising or whatever, or you're also selling a ton of lactic acid as a byproduct of glycolysis, be shipped that lactic acid to the liver, and then lactic dehydrogenase will convert that lactic acid to pyruvate, right? Remember, lactic dehydrogenase can work both ways. It's a bi-directional enzyme, and then that pyruvate, you know, through gluconeogenesis, you know, again, pyruvate carboxylase and then PPCK, and then all the way to glucose six phosphates, you make glucose, and then that glucose is shipped back to the muscles, right? For it to use. And also, that's a pathway that operates with red blood cells. Well, if by giving an hepatic gluconeogenesis, again, we talked about the mechanism of how melphormin ultimately leads to an inhibition of PPCK and glucose six phosphates, then you've essentially should circulate that Chorice cycle, right? So if you should circulate that Chorice cycle, you'll make sense that your lactic acid should build up because you don't have many pathways that can help you deal with that anymore, right? So lactic acid dose is a life threatening lactic acid doses. It's a big, big, big toxicity with melphormin. And melphormin, obviously, as well, you know, can cause a B12 deficiency, right? It actually, there are many different ways of meshes of B, causes B12 deficiency, like it can mess up intrinsic factor, it can mess up B12 reabsorption in the terminal helium, right?

It just does many different things, right? But melphormin can definitely cause a B12 deficiency. And another series of drugs, I guess, diabetes drugs, right? Those are P-PAR gamma activators, right? Those are your TC Ds, right? Your thiozolegging diodes, right? Again, the activities, the activities of P-PAR gamma, right? P-PAR gamma, and those these drugs, by the way, cause, cause weed gain, right? So P-PAR gamma, the thing with P-PAR gamma is that it's like a transcription factor, right? And it actually increases, like many, you know, it basically like causes you to, causes you have depo sites to work better, right? So they work better, because by activating P-PAR gamma, it actually, it's like a transcription factor that makes, how do I put this? It basically like increases the activity of certain enzymes that are necessary for fatty acid synthesis, right? So it's almost like, oh, you know, I have insulin resistance, but by using a different receptor, this P-PAR gamma receptor, I mean, by using, by activating P-PAR gamma, I'm essentially creating an alternate pathway for me to better utilize free fatty acids, right? So that I can store them. But again, if you notice, if you're making more and more fatty acids, making more and more triglycerides, that's going to make you fat, right?

These drugs, again, because weed gain, although they also cause fluid retention because they are P-PAR gamma receptors in the nephrine, which you know, causatory absorb more fluid, and as you hold on to that water, right? That's not great for pressing the HAS heart failure because their hearts cannot handle that increased fluid, right? So these P-PAR gamma activators, right? These are drugs like rosyclidazone, piochidazone, trochidazone, again, they are contraindicated in people that have CHF, right? And also you can see the name thia, zolydine dion, so the control like thiogrups, so your pressing has like a sulfur allergy, maybe not the best, maybe not the best idea, to give these people thiazolydine dions. And also sulfur allergies are, you know, not the greatest for food that they can solve for nail-eureus, right? So you don't want to give sulfur new areas, very the first generation ones, those are not good, those are bad, bad, bad, bad, people that have sulfur allergies, right? So just again, things to kind of keep at the back of your mind on exams. I guess since I've kind of talked about most of the diabetes drugs, maybe let me just maybe mention the rest, so that I know that I'm done with this section of conversation, but again, there is many, many, many more things that I really want to say with diabetes.

Again, this may be a tour, three-part podcast, but again, I know you may be like, well, the diabetes is a small topic, but again, you see I'm integrating many other things that are USMLE relevant, right? So let's talk about the remaining diabetes drugs, right? So remember, they are the alpha glucositis inhibitors, because remember, you're intestinal interro sites, they cannot reabsorb monosaccharides, I mean, sorry, they cannot reabsorb like saccharides, they can only reabsorb monosaccharides, right? So the thing is, there is a dysaccharide, you have dysaccharides on your brush border that brings down these dysaccharides to monosaccharides, right? So you can give a dysaccharide is inhibitor, right? Alpha glucositis is literally a dysaccharide is, so if you give an alpha glucositis inhibitor, right? That will essentially inhibit that dysaccharides on your brush border, so many times on exams, they can ask you, oh, what's the side of action of these alpha glucositis inhibitors, like, you know, acrobose and miglitol, again, they work on the brush border, so you won't be able to break down your dysaccharides, so they will sting the GI tract, they will attract fluid, right?

So that can cause diarrhea, but in addition to causing diarrhea, remember, as glucose stays in your, as those dysaccharides, they in your GI tract, you're essentially creating things given in your GI tract for those bacteria, so as the, as the bacteria consumes those, consumes those, the dysaccharides, they form all these gases, right? Through fermentation, so you get a lot of bloating, a lot of flatulence, right? But then another glucose set of drugs, right? Are those SGLT2 inhibitors, right? So they all end in flosing, right? Can I get flosing? Dapagli flosing, empagli flosing. Those drugs, right? The inhibitor, the SGLT2 receptors, that we find in the proximal convoluted tubule, right? So by inhibiting those receptors, glucose is going to sting your, on the urine side of your nephrons, and that's going to attract water, and you're going to peel those things out. In fact, these drugs actually help with weight loss, right? But again, you can already begin to see that if a person's kidneys don't work, because these drugs, they literally have to be filtered at the glomerulus, right? And then, they then attack your proximal tubules, that's how they work, right? So if a person's kidneys don't work at baseline, well, your GFR is not great, right? So you're not going to be able to filter those drugs into the nephron, right? So they're going to get less effectiveness, right?

But also, again, these drugs, because they put so much glucose in your urine, you can already begin to see that, again, you can have like an increased risk of urinary tract infections, you can even have like an acryptus of the perineum, right? That's what's called phonies, F-O-U-R, N-I-E-R, with an apostrophe and an S, right? Phonies can green, right? So those drugs are kind of dangerous from that perspective, although they also reduce the presence of myocardial infarction risk, because myocardial infarction, if you can do anything to decrease the risk in diabetics, that's a great thing, right? M-I is actually the most common cause of death in diabetics, right? That's like a very nice high-eal step 2, C-K, step 3 factor, the most common cause of death in diabetics is an acute M-I, right? So I'm going to go ahead and pause here. Again, as I do at the end of every podcast, I do offer 101 tutoring for many exams, step 1, step 2, C-K, step 3, pre-clean school med school exams, 30-ish-off exams, and if you're a medicine resident, and you need tutoring for your internal medicine and training exam, or you're internal medicine boards, I do offer tutoring for that. And again, I've talked about the step 2 C-K courses, I hold, and step 1, again, step 1, a lot of what I do now is one on one tutoring, just again, scheduling and things, but I really plan to, you know, hopefully in the future, hold a step 1 course around you, right?

So if you're interested in that, just shoot me an email, and I can do some more details on that. And then, I have a You Tube channel, Divine Intervention, USMD Podcasts, and videos, so please subscribe to that, that's where I post the videos that I make. And then I also have these podcasts, sonapo podcasts, Google podcasts, Spotify, at least the most recent 150. It's completely out of my hands, it's like a Word Press role, it's not much I can do about that. So if you want all the episodes that I've made from Episode 1, go ahead and go to my website, all the episodes are there, right? And you can even download the episodes there, and by the way, the website is Divine Intervention Podcast.com. If you go there, if you subscribe to the Word Press website, then whenever I make a new podcast, you'll get an email notification, right? You get an email notification. So I'll just encourage you to subscribe again so that you can get that notification whenever I make a, whenever I make a podcast. So I want to go ahead and discuss a quick life lesson this morning, and it's this statement that many can commit, but feel faithful, right? I'll say that again, many can commit, but feel faithful, right? Many can commit, but feel faithful, right? So the thing is, many people make commitments, and again, many times when I bring these life lessons, right? Obviously they're probably relevant to most people in this world, but they're especially relevant to match students, right?

So the thing is, there's a big difference between making a commitment and then being faithful to that commitment, right? The thing is, if you make a commitment, you're like, okay, yes, I'll do this, yes, I'll do that, yes, I'll do that, right? But after you make that commitment, you really follow through, right? Many can commit, but feel faithful. Commitment is cheap. You can get a commitment from someone, right? But how many people actually follow through on their commitments, right? You see some people, they come into a med school, they have a solid plan, solid solid plan for how to crush and kill step one, right? But if you don't follow through, right? They make that commitment, but then they are not disciplined, right? Really, to be a faithful person is, you're basically a person that sticks with your commitments, right? Those people, they just don't stick it through, right? They never never stick it through, right? And then you notice the end of the second year comes, the botched step one. And after the botched step one, they have this magic thought that they will crush step two. Again, it's possible. I mean, there are many people that have worked with that. They didn't dwell on step one, but again, how to work with them extensively and then they crush step two, right? But the thing is, many times one of the most important predictors of step two CK performance, guess what? It's step one performance. That's why I won't tell people when they make step one pass fail.

It should still study hard for it. If not, you'll find out that you botched step two, right? So, you know, you got to follow through on your commitments. You can just make commitments and just not keep them, right? Even in the Bible, he says that if you make a vow, you know, you should follow through on your vow, right? God does not have any pleasure in foods, right? Literally, that's what God calls people that don't keep their vow, right? So be faithful, right? When you make commitments, when you have a good solid plan, don't keep changing that plan because you saw someone else doing something new. No, no, no, just stay faithful, right? I mean, like one of the reasons that a marriage lasts is because, you know, because again, many people, they make these marriage commitments. Oh, I do. I will live with you for the rest of my life in sickness and in health, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, blah, right? You make all those commitments, right? But again, faithfulness is the thing that will then keep that marriage going, right? Again, you see many people, they invest so much in the wedding day. Again, there's nothing wrong with investing wedding day, right? Wedding day is the day of commitment, right? But then your actual marriage is the faithfulness part of things, right? Again, faithfulness is the thing that keeps a marriage going, right? Faithfulness, right?

And again, you know, being faithful is not the easiest thing in the world because there will be many challenges that arise, right? Like, when you make a commitment, that commitment is going to be tested. If you make a commitment and there's literally like no testing, you didn't make the right kind of commitment, right? Most times when you make a commitment, a challenge will show up, right? But again, you need to stay faithful through all those vicissitudes, all those problems, right? Like in any marriage, right? There's going to be probably there's there's no perfect marriage. There's going to be problems in any marriage, right? Even on the one of marriage, you may quarrel with your life partner with your spouse or whatever, right? But again, you've made a commitment now be faithful to that commitment, right? Again, that's the thing. That's why the fact that a wedding is, oh, wow, they spent tons and tons of money on the wedding. It's in the nicest part of town. It's in a great hall. Two million people came for the wedding. It doesn't matter. It doesn't do deadly squirt for that wedding, right? If the people that make that commitment are not faithful, right? If the people that make that commitment are not faithful, that's why even the Bible says that he that end yours to the end is the one that will be saved, right? The person that is literally like, because again, it's very easy to commit your life to Jesus. Jesus accepts you as my lord and savior.

And again, obviously, you need to take that first step, right? But again, you need to endure to the end to get that self to be, you know, to make it to heaven, right? So that's the thing, right? Like you need to stay faithful. Again, commitment is cheap, but faithfulness is expensive, right? And again, there are not many people that are faithful. In fact, if you're trying to hire someone, right? Always try to look for that characteristic of faithfulness because those people, right, they will follow through on their commitment, right? They'll follow through on their commitments. Again, faithfulness is not something that is exactly priced in this world we live in today, which is really sad because it's getting it's a very key component of being successful in life. But you know, again, that's a different conversation. But again, I'm just saying as a met student as a healthcare professional, right? If you've made a commitment, stay faithful to it. That faithfulness is the thing that will give you results from those commitments that you have made. So thank you for listening to this. I hope you've enjoyed this podcast. There will definitely be a part two. That's probably going to be the next podcast. So thank you for listening. I'll see you next time. God bless you. Thank you.

Polydipsia (excessive thirst), polyuria (frequent urination), and polyphagia (excessive hunger).

When blood glucose exceeds the proximal convoluted tubule's transport maximum (SGLT2 receptors, ~180 mg/dL), glucose spills into the urine, drawing water with it (osmotic diuresis).

Autoimmune destruction of pancreatic beta cells due to a failure of immune tolerance.

CTLA4 (Cytotoxic T-lymphocyte-associated protein 4).

GLP-1 (Glucagon-like peptide-1), acting via the incretin effect.

Sulfonylureas (e.g., glipizide).

Activates AMP kinase to inhibit hepatic gluconeogenesis by targeting PEPCK and Glucose-6-phosphatase.

SGLT2 inhibitors (e.g., dapagliflozin).

Failure of C-peptide levels to rise after glucagon infusion, indicating beta cell destruction.

Glucagon, Epinephrine, Cortisol (Glucocorticoids).

Increased gluconeogenesis; cortisol is a diabetogenic hormone.

Alpha-glucosidase inhibitors (e.g., acarbose).

Increased risk of Fournier's gangrene and potential for euglycemic diabetic ketoacidosis (though not explicitly stated, it is a key association).

Because the pancreatic beta cells are destroyed and cannot synthesize or release insulin.

Glucose-6-phosphatase (and Pyruvate Carboxylase).

Failure of C-peptide levels to rise after glucagon infusion, indicating beta cell destruction.

Glucagon, Epinephrine, Cortisol (Glucocorticoids).

Increased gluconeogenesis; cortisol is a diabetogenic hormone.

Alpha-glucosidase inhibitors (e.g., acarbose).

Increased risk of Fournier's gangrene and potential for euglycemic diabetic ketoacidosis (though not explicitly stated, it is a key association).

Because the pancreatic beta cells are destroyed and cannot synthesize or release insulin.

Glucose-6-phosphatase (and Pyruvate Carboxylase).